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Barium Evokes Glutamate Release from Rat Brain Synaptosomes by Membrane Depolarization: Involvement of K + , Na + , and Ca 2+ Channels
Author(s) -
Sihra Talvinder S.,
Piomelli Daniele,
Nichols Robert A.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb13612.x
Subject(s) - depolarization , synaptosome , biophysics , glutamate receptor , divalent , tetrodotoxin , chemistry , membrane potential , calcium , cytosol , barium , membrane , biochemistry , biology , inorganic chemistry , receptor , organic chemistry , enzyme
During K + ‐induced depolarization of isolated rat brain nerve terminals (synaptosomes), 1 m M Ba 2+ could substitute for 1 m M Ca 2+ in evoking the release of endogenous glutamate. In addition, Ba 2+ was found to evoke glutamate release in the absence of K + ‐induced depolarization. Ba 2+ (1–10 m M ) depolarized synaptosomes, as measured by voltage‐sensitive dye fluorescence and [ 3 H]‐tetraphenylphosphonium cation distribution. Ba 2+ partially inhibited the increase in synaptosomal K + efflux produced by depolarization, as reflected by the redistribution of radiolabeled 86 Rb + . The release evoked by Ba 2+ was inhibited by tetrodotoxin (TTX). Using the divalent cation indicator fura‐2, cytosolic [Ca 2+ ] increased during stimulation by approximately 200 n M , but cytosolic [Ba 2+ ] increased by more than 1 μ M . Taken together, our results indicate that Ba 2+ initially depolarizes synaptosomes most likely by blocking a K + channel, which then activates TTX‐sensitive Na + channels, causing further depolarization, and finally enters synaptosomes through voltage‐sensitive Ca 2+ channels to evoke neurotransmitter release directly. Though Ba 2+ ‐evoked glutamate release was comparable in level to that obtained with K + ‐induced depolarization in the presence of Ca 2+ , the apparent intrasynaptosomal level of Ba 2+ required for a given amount of glutamate release was found to be several‐fold higher than that required of Ca 2+ .